Development of a new therapy for immune related dry eye disease using senolytic reagents

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K09421
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Keio University
• Principal Investigator: OGAWA Yoko 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (30160774)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: ドライアイ / 眼移植片体宿主病 / 造血幹細胞移植 / 老化細胞 / マクロファージ / 老化細胞除去剤 / 線維化抑制 / 炎症抑制

Outline of Final Research Achievements

Aging in immune system is thought to be a factor in the development of chronic ocular GVHD, which is currently treated primarily with immunosuppressive therapies. Our findings suggest a potential association between chronic ocular GVHD pathogenesis and stress-induced cellular senescence through the senescence-associated secretory phenotype (SASP). Senescent cells produce cytokines and chemokines, such as IL-6 and CXCL9 a major components of SASP. Senescent cell accumulation was presumably associated with cGVHD development in lacrimal glands(LGs), as evidenced by the improvement in LGs after the selective elimination of senescent cells (senolysis) with ABT-263. Results in the sclerodermatous cGVHD mouse model suggest that inhibiting the SASP, including IL-6 and CXCL9, with senolytics is a potential novel strategy for treating cGVHD-affected LGs.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

免疫老化を軸に考えたGVHDによるドライアイおよび全身GVHDに対し,抗加齢治療として全く新しい病態解明と治療法開発の観点からすすめる研究はこれまでになく、学術的独自性と意義があると考える。本研究成果は、GVHDの病態が自己免疫疾患に類似するため広く自己免疫疾患による重症ドライアイの病態解明と抗加齢療法としての観点からの治療法の開発にも繋がる可能性がある。重症ドライアイの疾病予防のみならず老化細胞除去による病態解明が広く自己免疫疾患や加齢性疾患の病態解明につながり、健康寿命の延長に貢献する可能性がある点に学術的意義や社会的意義があると考える。